To date, various preparation processes of optically-active alcohols using metal complexes as a catalyst have been reported. In particular, processes in which optically-active alcohols are synthesized from ketone compounds by a reductive process using ruthenium complexes as a catalyst under the presence of base have been actively investigated. These processes are classified into “asymmetric hydrogenation” wherein hydrogen is used as a hydrogen source, and “asymmetric reduction” wherein organic substances and metal hydrides are used as a hydrogen source; their characteristics are as follows.
With respect to asymmetric hydrogenation wherein optically-active alcohols are obtained from ketones by asymmetric hydrogenation using hydrogen as a reducing agent, and to catalysts used therein, for example, JP No. 2731377 reports a case wherein an optically-active alcohol was prepared by hydrogenation of a ketone compound under the presence of base, using a catalyst consisting of a complex in which BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) and DMF are coordinated to ruthenium and of a diphenylethylenediamine ligand. While this catalyst had an extremely high activity, it had problems regarding the applicability to ketone substrates, namely, that the hydrogenation reaction did not progress efficiently or the enantiomeric excess was insufficient depending on the structure of the ketone compound. Therefore, catalysts with different structures have been developed with the aim of expanding the range of applicable ketone substrates.
For example, reactions of α-chloroketones (Org. Lett. Vol. 9, p. 255 (2007)) and 4-chromanone (J. Am. Chem. Soc. Vol. 128, p. 8724 (2006)) using a ruthenium catalyst having TsDPEN (N-(p-toluenesulfonyl)-1,2-diphenylethanediamine) as a ligand, and asymmetric hydrogenation of α-hydroxyketone using an iridium catalyst having MsDPEN (N-methanesulfonyl-1,2-diphenylethanediamine) as a ligand (WO 2006/137195, Org. Lett. Vol. 9, p. 2565 (2007)) have been reported. With these catalyst systems, there is no need to add bases, so that the kind of ketone substrates that can be used for reactions has been expanded. However, there are still many ketone substrates with which hydrogenation is difficult. In addition, these catalyst systems are easily affected by slight amounts of impurities contained in ketone substrates, which is problematic when actual industrial application is considered.
Meanwhile, asymmetric reduction systems have been developed to obtain optically-active alcohols by asymmetric reduction of ketones using organic substances such as formate and sodium formate as a hydrogen source. Since these catalyst systems do not use hydrogen gas, and do not require a pressure-resistant container, there is only a few limitation in production equipments; therefore, a number of reports have been published. In particular, in cases of asymmetric ruthenium catalysts that have a diamine ligand having a sulfonyl amide group as an anchor (JP No. 2962668), since a wide range of ketones can be asymmetrically reduced compared to hydrogenation catalysts, their performance is particularly notable. There are also several reports on rhodium catalysts and iridium catalysts that have a diamine ligand with the same structure (WO 98/42643, JP A No. 11-335385, Chem. Lett. p. 1199 (1998), Chem. Lett. p. 1201 (1998), J. Org. Chem. Vol. 64, p. 2186 (1999)). These rhodium and iridium catalysts have characteristic catalytic performances, and they are reported to exhibit significant effects on asymmetric reduction of imines (WO 00/56332) and α-haloketone (WO 2002/051781).
With respect to reactions wherein formate is used as a hydrogen source, there are reports on asymmetric reduction of aromatic ketones such as acetophenones, indanone and acetonaphtone under the presence of asymmetric ruthenium catalyst (Org. Biomol. Chem. Vol. 2, p. 1818 (2004)), and asymmetric reduction of ketones using asymmetric rhodium and iridium catalysts (Chem. Commun. p. 4447 (2005)).
With these catalyst systems however, catalytic performance such as catalytic efficiency and enantioselectivity in most cases were lower than those of hydrogenation catalysts, causing a significant problem. In cases where formate is used, problems of catalytic efficiency and substrate specificity have been resolved to some extent, but enantioselectivity is hardly improved.
To solve the above-mentioned various problems of asymmetric reduction catalyst systems, improvement of catalytic structure has been investigated. As a complex having CsDPEN (N-camphorsulfonyl-1,2-diphenylethylenediamine) as a ligand, JP. No. 3040353 discloses a ruthenium complex, and JP. A. No. 11-335385 discloses a rhodium complex and an iridium complex. An example wherein a complex having CsDPEN as a ligand is applied to the preparation of a duloxetine derivative has been disclosed (WO 2004/024708). In addition, a reaction wherein formate is used as a hydrogen source and a rhodium or iridium complex having a CsDPEN ligand is used as a catalyst has been reported in WO 2006/067395 and Synlett p. 1155 (2006). With these methods using CsDPEN complexes, the enantioselectivity has been improved compared to conventional hydrogen-transfer catalysts; however, in some cases the enantioselectivity is not sufficient depending on the structure of substrates. One such example includes a case of preparation of 3′,5′-bis(trifluoromethyl)acetophenone by means of two-phase asymmetric reduction using Cp*RhCl(Csdpen) as a catalyst and sodium formate as a hydrogen source; here, its optical purity is at the highest 83.0% ee (WO 2006/067395).
In the case of 2′-methoxyacetophenone, even when it was prepared by two-phase asymmetric reduction using Cp*IrCl (Csdpen) (Cp represents cyclopentadienyl group) as a catalyst and sodium formate as a hydrogen source, its optical purity was at the highest 85.0% ee (Synlett p. 1155 (2006)). Moreover, applicable substrates in these reports are limited to acetophenones having a substituent, and the range of applicable ketone substrates is not expanded. In addition, because camphor groups are an optically-active substance, it is difficult and costly to obtain a large amount of camphor groups. In addition, since CsDPEN has three asymmetric sites, its cost as a ligand and a complex becomes rather expensive, directly resulting in an increase in the cost of preparation process of optically-active alcohols, so that the industrial utility of this catalyst has been largely limited.
Other than those described above, WO 2007/120824 describes, as a catalyst used for the reduction of ketones in the synthesis of ezetimibe, a catalyst (Example 30) wherein [RuCl2(p-cymene)]2 and (S,S)-Bn-SO2-DPEN are combined, and a catalyst (Example 48) wherein [RuCl2(mesitylene)]2 and (S,S)-i-Bu-SO2-DPEN are combined. However, the applicable substrate range of these catalysts is narrow, and their enantioselectivity is low compared to CsDPEN complexes; accordingly, they are not sufficient for the application to the industrial preparation of optically-active alcohols.
As described above, with respect to the asymmetric hydrogenation catalysts which have been reported to date, the structure of applicable ketone substrates has been significantly limited; with respect to the asymmetric reduction catalysts, while the kind of applicable ketone substrates has been fairly expanded, it is not yet sufficient and their catalytic efficiency is problematic. CsDPEN complex catalysts which have been developed to overcome such problems are also practically insufficient in terms of cost and catalytic performance. Accordingly, the development of an inexpensive catalyst that can convert, with high enantioselectivity and high efficiency, ketones having various functional groups into optically-active alcohols, as well as a process for the preparation using said catalyst, have been desired.